An inducible chaperone adapts proteasome assembly to stress.

An inducible chaperone adapts proteasome assembly to stress.
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诱导的伴侣会适应蛋白酶体的组装应力。

DOI:
10.1016/j.molcel.2014.06.017
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发表时间:
2014-08-21
期刊:
影响因子:
16
通讯作者:
Bertolotti, Anne
Bertolotti, Anne
中科院分区:
生物学1区
文献类型:
--
作者:
Hanssum, Ariane;Zhong, Zhen;Rousseau, Adrien;Krzyzosiak, Agnieszka;Sigurdardottir, Anna;Bertolotti, Anne

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蛋白酶体对于大多数细胞蛋白质的选择性降解是必不可少的。为了在环境胁迫期间对蛋白酶体的巨大需求中生存下来,细胞增加了蛋白酶体的丰度。蛋白酶体的组装是已知的复杂过程。应激细胞是如何克服这一关键挑战的,目前尚不清楚。在旨在挽救酵母Rpt6温敏蛋白酶体突变体缺陷的无偏抑制筛选中,我们鉴定了一种蛋白质,以下命名为Adc17,因为它具有ATPase专属伴侣的功能。Adc17与Rpt6的氨基末端相互作用,帮助形成Rpt6-Rpt3 ATPase对,这是蛋白酶体组装的早期步骤。Adc17对细胞的适合性很重要,它的缺失会加剧蛋白酶体缺陷。Adc17的丰度随着蛋白酶体压力的增加而增加,其功能对维持蛋白酶体的稳态水平至关重要。因此,当需求增加时,细胞具有调节蛋白酶体组装的机制,而Adc17是这一过程的关键效应器。维持足够水平的蛋白酶体是至关重要的,当需求增加时,细胞增加蛋白酶体的丰度Adc17是一种可诱导的伴侣,它使蛋白酶体组装适应增加的需求Adc17协助Rpt6和Rpt3配对,这是蛋白酶体组装细胞增加蛋白酶体丰度的早期步骤,以便在环境应激中生存。Hanssum等人。揭示了控制蛋白酶体丰度的机制,表明Adc17是应激过程中蛋白酶体组装所需的可诱导伴侣。
The proteasome is essential for the selective degradation of most cellular proteins. To survive overwhelming demands on the proteasome arising during environmental stresses, cells increase proteasome abundance. Proteasome assembly is known to be complex. How stressed cells overcome this vital challenge is unknown. In an unbiased suppressor screen aimed at rescuing the defects of a yeast Rpt6 thermosensitive proteasome mutant, we identified a protein, hereafter named Adc17, as it functions as an ATPase dedicated chaperone. Adc17 interacts with the amino terminus of Rpt6 to assist formation of the Rpt6-Rpt3 ATPase pair, an early step in proteasome assembly. Adc17 is important for cell fitness, and its absence aggravates proteasome defects. The abundance of Adc17 increases upon proteasome stresses, and its function is crucial to maintain homeostatic proteasome levels. Thus, cells have mechanisms to adjust proteasome assembly when demands increase, and Adc17 is a critical effector of this process. The maintenance of adequate levels of proteasome is vital Cells increase proteasome abundance when the needs increase Adc17 is an inducible chaperone that adapts proteasome assembly to increased needs Adc17 assists the pairing of Rpt6 and Rpt3, an early step in proteasome assembly Cells increase proteasome abundance in order to survive during environmental stress. Hanssum et al. reveal a mechanism for controlling proteasome abundance, showing that Adc17 is an inducible chaperone needed for proteasome assembly during stress.
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